Asthma/COPD:

Indications for: PULMICORT FLEXHALER

Maintenance treatment of asthma as prophylactic therapy. Asthma requiring systemic corticosteroid therapy, to reduce need for systemic corticosteroids.

Clinical Trials:

The efficacy of Pulmicort Flexhaler was evaluated in two 12-week, double-blind, randomized, parallel-group, placebo-controlled clinical studies (Study 1 and Study 2) which included 1137 patients aged 6 to 80 years with mild to moderate asthma. Both studies had a 2-week placebo treatment run-in period followed by a 12-week randomized treatment period. The primary endpoint was the difference between baseline and the mean of the treatment-period FEV1 (adults) or FEV1% predicted (children).

 

Study 1 (Patients aged ≥18 years)

  • The study included 621 patients 18 to 80 years of age with mild to moderate asthma previously treated with inhaled corticosteroids.

  • Patients were randomly assigned to receive either Pulmicort Flexhaler 180mcg, Pulmicort Turbuhaler 200mcg, or placebo administered as 1 inhalation once daily or 2 inhalations twice daily.

  • Results showed that patients treated with Pulmicort Flexhaler 180mcg (2 inhalations twice daily) achieved a mean change from baseline in FEV1 of 0.28 liters compared with 0.10 liters in the placebo arm (P <.001).

  • Patients treated with Pulmicort Flexhaler also met secondary endpoints of morning and evening peak expiratory flow rate, daytime asthma symptom severity, nighttime asthma symptom severity, and daily rescue medication use compared with placebo (P <.001).

 

Study 2 (Patients aged 6 to 17 years)

  • The study included 516 patients 6 to 17 years of age and older with mild to moderate asthme previously treated with inhaled corticosteroids.

  • Patients were randomly assigned to receive either Pulmicort Flexhaler 90mcg 2 inhalations twice daily or 4 inhalations twice daily; or Pulmicort Turbuhaler 200mcg 1 inhalation once daily or 2 inhalations twice daily; or placebo.

  • Results showed that patients treated with Pulmicort Flexhaler 90mcg 4 inhalations twice daily achieved a mean change from baseline in % predicted FEV1 of 5.6 compared with 0.2 in the placebo arm (P <.001).

  • Patients treated with Pulmicort Flexhaler also met secondary endpoints of morning and evening PEF compared with placebo (P <.001).

Adult Dosage:

≥18yrs: Initially 360mcg twice daily; may consider starting at 180mcg twice daily, if appropriate. Max 720mcg twice daily. Rinse mouth after use.

Children Dosage:

<6yrs: not established. ≥6yrs: Initially 180mcg twice daily; may consider starting at 360mcg twice daily, if appropriate. Max 360mcg twice daily. Rinse mouth after use.

PULMICORT FLEXHALER Contraindications:

Not for primary treatment of acute attack.

PULMICORT FLEXHALER Warnings/Precautions:

Maintain regular regimen. Infections. If exposed to chickenpox or measles, consider antiinfective prophylactic therapy. Adrenal insufficiency may occur when transferring patients from systemic corticosteroids to inhaled corticosteroids: see full labeling. Monitor for growth suppression in children. Post-op or during stress: monitor adrenal response. Monitor for hypercorticism and HPA axis suppression (if occur discontinue gradually). Transferring from oral corticosteroids: see full labeling. Pregnancy. Nursing mothers.

See Also:

PULMICORT FLEXHALER Classification:

Steroid.

PULMICORT FLEXHALER Interactions:

Caution with CYP3A4 inhibitors (eg, ketoconazole, itraconazole, atazanavir, ritonavir, indinavir, nefazodone, nelfinavir, saquinavir, clarithromycin, telithromycin).

Adverse Reactions:

Pulmicort Flexhaler: nasopharyngitis, nasal congestion, pharyngitis, allergic rhinitis, viral upper respiratory tract infection, oral candidiasis, viral gastroenteritis, nausea, otitis media, bronchospasm (rare). Pulmicort Respules: Respiratory or other infection, GI upset, moniliasis, fatigue, cough, dysphonia, rash, epistaxis, hypersensitivity reactions (discontinue if occurs).

Metabolism:

In vitro studies with human liver homogenates have shown that budesonide is rapidly and extensively metabolized. Two major metabolites formed via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) catalyzed biotransformation have been isolated and identified as 16α-hydroxyprednisolone and 6β-hydroxybudesonide. The corticosteroid activity of each of these two metabolites is less than 1% of that of the parent compound. No qualitative difference between the in vitro and in vivo metabolic patterns has been detected. Negligible metabolic inactivation was observed in human lung and serum preparations. 

Drug Elimination:

Budesonide is primarily cleared by the liver. Budesonide is excreted in urine and feces in the form of metabolites. In adults, approximately 60% of an intravenous radiolabeled dose was recovered in the urine. No unchanged budesonide was detected in the urine. In asthmatic children 4-6 years of age, the terminal half-life of budesonide after nebulization is 2.3 hours, and the systemic clearance is 0.5 L/min, which is approximately 50% greater than in healthy adults after adjustment for differences in weight. 

Generic Drug Availability:

Flexhaler (NO); Respules (YES)

How Supplied:

Flexhaler (90mcg/dose)—1 (60 inh); Flexhaler (180mcg/dose)—1 (120 inh); Respules—30